Multiple sclerosis (MS) is a disease in which immune mechanisms may be playing a significant etiologic role. It is hypothesized that a possible antigen evoking this autoimmune response is a fetal brain antigen. To test this hypothesis I propose to look for fetal brain antigen in serum and cerebrospinal fluid (CSF) from patients with MS, as well as for the presence of an immune response against fetal brain antigens. To look for the presence of fetal brain antigen extracts will be prepared from the brains of three to four month old human abortuses. Suitably absorbed rabbit antisera to these extracts will be prepared. By the use of a coprecipitation-inhibition assay using isotopically labeled fetal brain extract and rabbit antiserum fetal brain antigen present in the human patient serum of CSF will be determined. The presence of both cellular and humoral forms of immune responses against fetal brain antigens will be evaluated. To look for cellular immune responses monolayer cultures of fetal brain cells will be exposed to purified populations of lymphocytes from patients wih MS. The cultures will be evaluated for the presence of glial cell killing by lymphocytes. In addition, the proliferative response of MS patients' lymphocytes to exposure to either fetal brain cultures of fetal brain extracts will be measured. Humoral antibody against feta brain antigen will be determined by radioimmunoelectrophoresis utilizing isotopically labeled fetal brain extract, patient serum or CSF and anti-human gamma globulin antiserum. In addition, fetal brain cultures will be coated with patients' serum or CSF and the presence of immunoglobulin binding to these monolayers determined by subsequent addition of fluoresceinlabeled goat anti-human gamma globulin antiserum.